tbuckley/cabot-search huggingface dataset:
Dopamine signaling in the nucleus accumbens core mediates latent inhibition
Authors: Munir Gunes Kutlu, Jennifer E. Zachry, Patrick R. Melugin, Jennifer Tat, Stephanie Cajigas, Atagun U. Isiktas, Dev D. Patel, Cody A. Siciliano, Geoffrey Schoenbaum, Melissa J. Sharpe, Erin S. Calipari
Journal: Nature Neuroscience (2022)
Nationwide gastric cancer prevention in China, 2021–2035: a decision analysis on effect, affordability and cost-effectiveness optimisation
Authors: Zixing Wang, Wei Han, Fang Xue, Yujie Zhao, Peng Wu, Yali Chen, Cuihong Yang, Wentao Gu, Jingmei Jiang
Journal: Gut (2022)

Objective To project future trajectories of the gastric cancer (GC) burden in China under different scenarios of GC prevention and identify strategies to improve affordability and cost-effectiveness. Design Using a cohort of Chinese men and women born during 1951–1980, we assumed that different prevention strategies were conducted, including eradication of Helicobacter pylori (Hp) and endoscopy screening (one-time, annual, biennial, triennial or stratified according to personal risk). We performed a literature search to identify up-to-date data and populate a Markov model to project the number of new GC cases and deaths during 2021–2035, as well as resource requirements and quality-adjusted life-years (QALYs). We examined the impacts of general (among the whole population) and targeted (high-risk population) prevention. Results During 2021–2035, 10.0 million new GC cases and 5.6 million GC deaths would occur, with 7.6%–35.5% and 6.9%–44.5%, respectively, being avoidable through various prevention strategies. Relative to the status quo, Hp eradication was a cost-saving strategy. General annual screening dominated other screening strategies, but cost more than CNY 70 000 per QALY gained (willingness-to-pay) compared with Hp eradication. Among endoscopy strategies, targeted screening resulted in 44%–49% lower cost per QALY gained over the status quo than general screening. Among high-risk population, tailoring the screening frequency according to personal risk could reduce endoscopy-related resources by 22% compared with biennial screening and by 55% compared with annual screening, Conclusion Our findings provide important input for future decision-making and investment, highlighting the need and feasibility for China to include GC prevention in its national health plans.
Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet+ B cells
Authors: Krisztian Csomos, Boglarka Ujhazi, Peter Blazso, Jose L. Herrera, Christopher M. Tipton, Tomoki Kawai, Sumai Gordon, Maryssa Ellison, Kevin Wu, Matthew Stowell, Lauren Haynes, Rachel Cruz, Bence Zakota, Johnny Nguyen, Michelle Altrich, Christoph B. Geier, Svetlana Sharapova, Joseph F. Dasso, Jennifer W. Leiding, Grace Smith, Waleed Al-Herz, Mayra de Barros Dorna, Olajumoke Fadugba, Eva Fronkova, Veronika Kanderova, Michael Svaton, Sarah E. Henrickson, Joseph D. Hernandez, Taco Kuijpers, Snezhina Mihailova Kandilarova, Elizaveta Naumova, Tomas Milota, Anna Sediva, Despina Moshous, Benedicte Neven, Tara Saco, Ravishankar Sargur, Sinisa Savic, John Sleasman, Gauri Sunkersett, Brant R. Ward, Masanobu Komatsu, Stefania Pittaluga, Attila Kumanovics, Manish J. Butte, Michael P. Cancro, Shiv Pillai, Eric Meffre, Luigi D. Notarangelo, Jolan E. Walter
Journal: Nature Immunology (2022)

The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent 'domino effect' that impacts stringency of tolerance and B cell fate in the periphery.
Improving Outcomes in Schizophrenia—A Case for Initiation of Long-Acting Antipsychotics in Early-Phase Illness
Authors: Brittany M. Gouse, Hannah E. Brown
Journal: JAMA Network Open (2022)

Yue Wei, MPH; Vincent K. C. Yan, BPharm; Wei Kang, MSc; Ian C. K. Wong, PhD; David J. Castle, MD; Le Gao, MSc; Celine S. L. Chui, PhD; Kenneth K. C. Man, PhD; Joseph F. Hayes, PhD; Wing Chung Chang, MD; Esther W. Chan, PhD
Disparities in distribution of COVID-19 vaccines across US counties: A geographic information system–based cross-sectional study
Authors: Inmaculada Hernandez, Sean Dickson, Shangbin Tang, Nico Gabriel, Lucas A. Berenbrok, Jingchuan Guo
Journal: PLoS Medicine (2022)

The US Centers for Disease Control and Prevention has repeatedly called for Coronavirus Disease 2019 (COVID-19) vaccine equity. The objective our study was to measure equity in the early distribution of COVID-19 vaccines to healthcare facilities across the US. Specifically, we tested whether the likelihood of a healthcare facility administering COVID-19 vaccines in May 2021 differed by county-level racial composition and degree of urbanicity.
Fecal Metabolome and Bacterial Composition in Severe Obesity: Impact of Diet and Bariatric Surgery
Authors: Nuria Salazar, Manuel Ponce-Alonso, María Garriga, Sergio Sanchez-Carrillo, Ana María Hernández-Barranco, Begoña Redruello, María Fernández, José Ignacio Botella-Carretero, Belén Vega-Piñero, Javier Galeano, Javier Zamora, Manuel Ferrer, Clara G de Los Reyes-Gavilán, Rosa Del Campo
Journal: Gut Microbes (2022)

The aim of this study was to monitor the impact of a preoperative low-calorie diet and bariatric surgery on the bacterial gut microbiota composition and functionality in severe obesity and to compare sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB). The study also aimed to incorporate big data analysis for the omics results and machine learning by a Lasso-based analysis to detect the potential markers for excess weight loss. Forty patients who underwent bariatric surgery were recruited (14 underwent SG, and 26 underwent RYGB). Each participant contributed 4 fecal samples (baseline, post-diet, 1 month after surgery and 3 months after surgery). The bacterial composition was determined by 16S rDNA massive sequencing using MiSeq (Illumina). Metabolic signatures associated to fecal concentrations of short-chain fatty acids, amino acids, biogenic amines, gamma-aminobutyric acid and ammonium were determined by gas and liquid chromatography. Orange 3 software was employed to correlate the variables, and a Lasso analysis was employed to predict the weight loss at the baseline samples. A correlation between Bacillota (formerly Firmicutes) abundance and excess weight was observed only for the highest body mass indexes. The low-calorie diet had little impact on composition and targeted metabolic activity. RYGB had a deeper impact on bacterial composition and putrefactive metabolism than SG, although the excess weight loss was comparable in the two groups. Significantly higher ammonium concentrations were detected in the feces of the RYGB group. We detected individual signatures of composition and functionality, rather than a gut microbiota characteristic of severe obesity, with opposing tendencies for almost all measured variables in the two surgical approaches. The gut microbiota of the baseline samples was not useful for predicting excess weight loss after the bariatric process.
Bacterial-fungal metabolic interactions within the microbiota and their potential relevance in human health and disease: a short review
Authors: Alexia Lapiere, Mathias L Richard
Journal: Gut Microbes (2022)

The composition of the microbiota is the focus of many recent publications describing the effects of the microbiota on host health. In recent years, research has progressed further, investigating not only the diversity of genes and functions but also metabolites produced by microorganisms composing the microbiota of various niches and how these metabolites affect and shape the microbial community. While an abundance of data has been published on bacterial interactions, much less data are available on the interactions of bacteria with another component of the microbiota: the fungal community. Although present in smaller numbers, fungi are essential to the balance of this complex microbial ecosystem. Both bacterial and fungal communities produce metabolites that influence their own population but also that of the other. However, to date, interkingdom interactions occurring through metabolites produced by bacteria and fungi have rarely been described. In this review, we describe the major metabolites produced by both kingdoms and discuss how they influence each other, by what mechanisms and with what consequences for the host.
Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough
Authors: Rhianna E. Lee, Catherine A. Lewis, Lihua He, Emily C. Bulik-Sullivan, Samuel C. Gallant, Teresa M. Mascenik, Hong Dang, Deborah M. Cholon, Martina Gentzsch, Lisa C. Morton, John T. Minges, Jonathan W. Theile, Neil A. Castle, Michael R. Knowles, Adam J. Kimple, Scott H. Randell
Journal: Journal of Clinical Investigation (2022)

The vast majority of people with cystic fibrosis (CF) are now eligible for CF transmembrane regulator (CFTR) modulator therapy. The remaining individuals with CF harbor premature termination codons (PTCs) or rare CFTR variants with limited treatment options. Although the clinical modulator response can be reliably predicted using primary airway epithelial cells, primary cells carrying rare CFTR variants are scarce. To overcome this obstacle, cell lines can be created by overexpression of mouse Bmi-1 and human TERT (hTERT). Using this approach, we developed 2 non-CF and 6 CF airway epithelial cell lines, 3 of which were homozygous for the W1282X PTC variant. The Bmi-1/hTERT cell lines recapitulated primary cell morphology and ion transport function. The 2 F508del-CFTR cell lines responded robustly to CFTR modulators, which was mirrored in the parent primary cells and in the cell donors' clinical response. Cereblon E3 ligase modulators targeting eukaryotic release factor 3a (eRF3a) rescued W1282X-CFTR function to approximately 20% of WT levels and, when paired with G418, rescued G542X-CFTR function to approximately 50% of WT levels. Intriguingly, eRF3a degraders also diminished epithelial sodium channel (ENaC) function. These studies demonstrate that Bmi-1/hTERT cell lines faithfully mirrored primary cell responses to CFTR modulators and illustrate a therapeutic approach to rescue CFTR nonsense mutations.
Microbiota-derived metabolites as drivers of gut–brain communication
Authors: Hany Ahmed, Quentin Leyrolle, Ville Koistinen, Olli Kärkkäinen, Sophie Layé, Nathalie Delzenne, Kati Hanhineva
Journal: Gut Microbes (2022)

Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut–brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut–brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut–brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins
The Modular µSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro
Authors: Molly C. McCloskey, Pelin Kasap, S. Danial Ahmad, Shiuan‐Haur Su, Kaihua Chen, Mehran Mansouri, Natalie Ramesh, Hideaki Nishihara, Yury Belyaev, Vinay V. Abhyankar, Stefano Begolo, Benjamin H. Singer, Kevin F. Webb, Katsuo Kurabayashi, Jonathan Flax, Richard E. Waugh, Britta Engelhardt, James L. McGrath
Journal: Advanced Healthcare Materials (2022)

Advanced in vitro tissue chip models can reduce and replace animal experimentation and may eventually support "on-chip" clinical trials. To realize this potential, however, tissue chip platforms must be both mass-produced and reconfigurable to allow for customized design. To address these unmet needs, an extension of the µSiM (microdevice featuring a silicon-nitride membrane) platform is introduced. The modular µSiM (m-µSiM) uses mass-produced components to enable rapid assembly and reconfiguration by laboratories without knowledge of microfabrication. The utility of the m-µSiM is demonstrated by establishing an hiPSC-derived blood-brain barrier (BBB) in bioengineering and nonengineering, brain barriers focused laboratories. In situ and sampling-based assays of small molecule diffusion are developed and validated as a measure of barrier function. BBB properties show excellent interlaboratory agreement and match expectations from literature, validating the m-µSiM as a platform for barrier models and demonstrating successful dissemination of components and protocols. The ability to quickly reconfigure the m-µSiM for coculture and immune cell transmigration studies through addition of accessories and/or quick exchange of components is then demonstrated. Because the development of modified components and accessories is easily achieved, custom designs of the m-µSiM shall be accessible to any laboratory desiring a barrier-style tissue chip platform.
Sexual dysfunction and disorders as a consequence of infertility: a systematic review and meta-analysis
Authors: Brigitte Leeners, Sibil Tschudin, Tewes Wischmann, Dimitrios Rafail Kalaitzopoulos
Journal: Human Reproduction Update (2022)

Abstract BACKGROUND Sexuality has a key impact on quality of life and on reproductive health. Infertility often results in sexual dysfunction. Despite this close association, addressing sexuality is not a standard component of infertility counselling, especially since in most countries sexual medicine is not a core element of specialist training. Even today, many doctors and patients consider discussing sexuality to be more challenging than other aspects of reproductive medicine. The present review addresses the complex consequences of infertility on sexuality. OBJECTIVE AND RATIONALE Our goals were: (i) to identify the prevalence of sexual problems resulting from infertility, (ii) to evaluate characteristics of sexual difficulties and disorders resulting from infertility and (iii) to analyse factors involved in the complex association between sexual problems and infertility. SEARCH METHODS A systematic search for publications containing keywords related to sexual disorders and infertility was performed via PubMed, Web of Science and Psyndex. A total of 170 manuscripts published between January 1966 and April 2021 were identified after verification of inclusion and exclusion criteria. The reference lists in these manuscripts were searched for further relevant literature. Studies were reviewed for quality-related methodological details. OUTCOMES Couples diagnosed with infertility have an increased risk of sexual disorders. Loss of sexual desire and erectile dysfunction are among the most frequent sexual disorders resulting from infertility. Currently available literature reflects only fragmentarily the complexity of the diverse interactions. Sexuality plays out against the backdrop of interactions among personal, cultural, infertility-related and sexuality-related factors. Considering this complexity, it is crucial to evaluate individual profiles as well as partnership interactions to avoid a negative impact of infertility on a couple’s sexual life. WIDER IMPLICATIONS Identifying sexual disorders as relevant considerations in the context of infertility and exploring their impact during the entire course of diagnosis and treatment constitute an important contribution to comprehensively care for the couples concerned. Counselling should focus on preventing the onset and aggravation of sexual disorders. As sexuality represents a major component of quality of life and of partnership, such support may improve not only the current overall wellbeing but also the chances of a satisfactory long-term partnership and family life.
A Case of Catathrenia Captured on Polysomnography with Audio–Visual Recording
Authors: Anusha Devarajan, Miranda R. Roderick, Bernie W. Miller, Chad M. Ruoff
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"A Case of Catathrenia Captured on Polysomnography with Audio–Visual Recording." American Journal of Respiratory and Critical Care Medicine, 206(10), pp. 1281–1283
From novel discovery tools and biomarkers to precision medicine—basic cardiovascular science highlights of 2021/22
Authors: Paul C Evans, Sean M Davidson, Johann Wojta, Magnus Bäck, Sveva Bollini, Mairi Brittan, Alberico L Catapano, Bill Chaudhry, Matthijs Cluitmans, Massimiliano Gnecchi, Tomasz J Guzik, Imo Hoefer, Rosalinda Madonna, João P Monteiro, Henning Morawietz, Elena Osto, Teresa Padró, Judith C Sluimer, Carlo Gabriele Tocchetti, Kim Van der Heiden, Gemma Vilahur, Johannes Waltenberger, Christian Weber
Journal: Cardiovascular Research (2022)

Abstract Here, we review the highlights of cardiovascular basic science published in 2021 and early 2022 on behalf of the European Society of Cardiology Council for Basic Cardiovascular Science. We begin with non-coding RNAs which have emerged as central regulators cardiovascular biology, and then discuss how technological developments in single-cell ‘omics are providing new insights into cardiovascular development, inflammation, and disease. We also review recent discoveries on the biology of extracellular vesicles in driving either protective or pathogenic responses. The Nobel Prize in Physiology or Medicine 2021 recognized the importance of the molecular basis of mechanosensing and here we review breakthroughs in cardiovascular sensing of mechanical force. We also summarize discoveries in the field of atherosclerosis including the role of clonal haematopoiesis of indeterminate potential, and new mechanisms of crosstalk between hyperglycaemia, lipid mediators, and inflammation. The past 12 months also witnessed major advances in the field of cardiac arrhythmia including new mechanisms of fibrillation. We also focus on inducible pluripotent stem cell technology which has demonstrated disease causality for several genetic polymorphisms in long-QT syndrome and aortic valve disease, paving the way for personalized medicine approaches. Finally, the cardiovascular community has continued to better understand COVID-19 with significant advancement in our knowledge of cardiovascular tropism, molecular markers, the mechanism of vaccine-induced thrombotic complications and new anti-viral therapies that protect the cardiovascular system.
Listening to the Patient Voice Adds Value to Cancer Clinical Trials
Authors: Michael D Brundage, Norah L Crossnohere, Jennifer O’Donnell, Samantha Cruz Rivera, Roger Wilson, Albert W Wu, David Moher, Derek Kyte, Bryce B Reeve, Alexandra Gilbert, Ronald C Chen, Melanie J Calvert, Claire Snyder
Journal: JNCI Journal of the National Cancer Institute (2022)

Randomized clinical trials are critical for evaluating the safety and efficacy of interventions in oncology and informing regulatory decisions, practice guidelines, and health policy. Patient-reported outcomes (PROs) are increasingly used in randomized trials to reflect the impact of receiving cancer therapies from the patient perspective and can inform evaluations of interventions by providing evidence that cannot be obtained or deduced from clinicians' reports or from other biomedical measures. This commentary focuses on how PROs add value to clinical trials by representing the patient voice. We employed 2 previously published descriptive frameworks (addressing how PROs are used in clinical trials and how PROs have an impact, respectively) and selected 9 clinical trial publications that illustrate the value of PROs according to the framework categories. These include 3 trials where PROs were a primary trial endpoint, 3 trials where PROs as secondary endpoints supported the primary endpoint, and 3 trials where PROs as secondary endpoints contrast the primary endpoint findings in clinically important ways. The 9 examples illustrate that PROs add valuable data to the care and treatment context by informing future patients about how they may feel and function on different treatments and by providing clinicians with evidence to support changes to clinical practice and shared decision making. Beyond the patient and clinician, PROs can enable administrators to consider the cost-effectiveness of implementing new interventions and contribute vital information to policy makers, health technology assessors, and regulators. These examples provide a strong case for the wider implementation of PROs in cancer trials.
Associations Between State-Level Severe Maternal Morbidity and Other Perinatal Indicators
Authors: Ashley H. Hirai, Pamela L. Owens, Lawrence D. Reid, Catherine J. Vladutiu, Elliott K. Main
Journal: JAMA Network Open (2022)

This cross-sectional study examines state-level associations between severe maternal morbidity and other perinatal indicators, including prepregnancy hypertension, prepregnancy diabetes, prepregnancy obesity, low-risk cesarean delivery, preterm birth, and maternal and infant mortality.